Eli Lilly announced today that it was able to achieve positive results from two of its pivotal phase 3 studies using its once-weekly, triple hormone receptor agonist retatrutide for the treatment of patients with obesity. The two late-stage studies in question were TRIUMPH-2 and TRIUMPH-3. The notion for these studies was to help treat patients with obesity but also to target two different co-morbidities.

The phase 3 TRIUMPH-2 study was set to treat adults who were obese or overweight and who also had type 2 diabetes [T2D]. The other phase 3 study in question, TRIUMPH-3, recruited adults who were obese or overweight and who had cardiovascular disease. The premise here is that the company has already received regulatory approvals for two other weight loss drugs, which are Foundayo and Zepbound. Each of these therapies has been approved for weight loss and is given via oral administration and as an injection to patients, respectively.

Furthermore, Eli Lilly is not just developing a similar drug; it is expanding its presence in the obesity space. Foundayo [orforglipron] targets the glucagon-like peptide-1 [GLP-1] receptor and is given via oral administration. Zepbound [tirzepatide] targets two hormones, which are the GLP-1 receptor and the gastric inhibitory polypeptide [GIP] receptors. Having said that, retatrutide takes it one step further with an additional target of glucagon. Because of the three targets it has, it has been dubbed “triple-g.”

In the TRIUMPH-2 study, adults who are obese or overweight and have T2D were given 3 doses of retatrutide or placebo and evaluated for an 80-week period. During that period of time, the highest dose of 12 mg of the company’s therapy allowed patients to lose, on average, 49.6 lbs. [20.8%]. This is a good result, because it is not easy for this specific group of obesity patients to lose weight. Secondly, because such drugs like this help in terms of T2D, it also had an impact on reducing A1C from baseline, with the mid-level dose performing the best with a reduction of 1.6%.

The patients in the TRIUMPH-3 study were adults who were obese or overweight and who had cardiovascular disease. This study was also to evaluate such patients over an 80-week period. During such time, the highest dose of 12 mg of retatrutide was delivered again, allowing patients to lose an average of 55.8 lbs. [22.6%].

The downside, like all GLP-1 type drugs, is that they have a lot of side effects. The most common side effects that were experienced in both of these TRIUMPH studies were nausea, diarrhea, and constipation. The good news is that with positive data now obtained across 5 studies for this drug, it believes that it is going to be able to submit a Biologics License Application [BLA] to the FDA to receive approval of retatrutide for obese or overweight patients with co-morbidities.

With the tolerability profile for retatrutide, it won’t likely produce as much revenue as its other drugs, Foundayo and Zepbound. However, it is expected to capture a certain chunk of the obesity market. Specifically, a portion of patients who are in more dire need. Even then, the projections are sill good for this drug in terms of sales. In a note by TD Cowen, analysts estimated that could generate $3.8 billion in revenues in 2030.

The GLP-1 hormone receptor itself has two functions. It not only serves to deliver a message to the hypothalamus that a person is “full” but also causes a delay in gastric emptying. The GIP receptor improves fat metabolism and prevents storage of fat. Glucagon increases energy expenditure, having calories burned along with the liver getting rid of stored fat. As you saw above, these receptors together were able to produce significant weight loss for these two obesity populations with these specific co-morbidities of T2D and cardiovascular disease.